Nowadays, approximately 3% of the world’s population suffers from psoriasis, an inflammatory dermatosis with high recurrence. Tryptanthrin (TRYP) is a natural alkaloid that possesses anti-inflammatory activities on multiple diseases. The present study aimed to unravel whether TRYP could relieve psoriasis and how it works. Imiquimod (IMQ)-induced psoriatic mouse models were administered saline (model), TRYP (25 and 100 mg/kg), or methotrexate (MTX, 1 mg/kg) and considered as the positive control. TNF-α-induced keratinocytes (HaCaT cells) with TRYP (0, 10, 20 and 50 nM) were used for in vitro verification. Psoriasis area severity index (PASI) and spleen index were evaluated. Th17 cell infiltration in both spleens and lymph nodes was detected by flow cytometry. The expression levels of inflammatory cytokines, glutathione (GSH), malondialdehyde (MDA) and catalase (CAT), as well as superoxide dismutase (SOD), were examined by ELISA, while the NF-κB/MAPK/Nrf2 pathways-related proteins were determined by western blot. TRYP significantly attenuated psoriatic skin lesions, increased GSH, SOD, and CAT levels, reduced spleen index, accumulation of MDA, the abundance of Th17 cells in both the spleen and lymph nodes, and secretion of inflammatory cytokines in IMQ-induced psoriatic mouse models. Mechanically, TRYP suppressed IMQ-activated NF-κB (IκB and p65), MAPK (JNK, ERK1/2, and p38), and activated Nrf2 signaling pathways. Similar alterations for inflammation and oxidative stress parameters and NF-κB/MAPK/Nrf2 pathways were also observed in TNF-α-treated HaCaT cells upon TRYP treatment. Our findings suggested TRYP is effective in protecting against inflammation and oxidative stress in psoriasis-like pathogenesis by modulating the NF-κB/MAPK/Nrf2 pathways.

如今，世界上约有 3% 的人口患有银屑病，这是一种复发率高的炎症性皮肤病。色氨酸 (TRYP) 是一种天然生物碱，对多种疾病具有抗炎活性。本研究旨在阐明 TRYP 是否可以缓解银屑病及其作用机制。给予咪喹莫特 (IMQ) 诱导的银屑病小鼠模型生理盐水（模型）、TRYP（25 和 100 mg/kg）或甲氨蝶呤（MTX，1 mg/kg）并作为阳性对照。具有 TRYP（0、10、20 和 50 nM）的 TNF-α 诱导的角质形成细胞（HaCaT 细胞）用于体外验证。评估银屑病面积严重程度指数 (PASI) 和脾脏指数。通过流式细胞术检测脾脏和淋巴结中的 Th17 细胞浸润。炎性细胞因子、谷胱甘肽 (GSH) 的表达水平，丙二醛 (MDA) 和过氧化氢酶 (CAT) 以及超氧化物歧化酶 (SOD) 通过 ELISA 检测，而 NF-κB/MAPK/Nrf2 通路相关蛋白通过蛋白质印迹检测。TRYP 显着减轻银屑病皮肤损伤，增加 GSH、SOD 和 CAT 水平，降低脾脏指数，MDA 积累，脾脏和淋巴结中 Th17 细胞的丰度，以及 IMQ 诱导的银屑病小鼠模型中炎性细胞因子的分泌。从机械上讲，TRYP 抑制 IMQ 激活的 NF-κB（IκB 和 p65）、MAPK（JNK、ERK1/2 和 p38），并激活 Nrf2 信号通路。在 TRYP 处理后，在 TNF-α 处理的 HaCaT 细胞中也观察到炎症和氧化应激参数以及 NF-κB/MAPK/Nrf2 通路的类似改变。